Meiuaan Qian, Yuefefeng Tan, Bo xu
Isicelo se-R & D
Intshayelelo
I-TARUS (i-teksi i-chinenis okanye i-wew ye-yej) sisityalo sasendle esikhuselweyo lilizwe. Sisityalo esinqabileyo nesibeka emngciphekweni esisemva kweqhwa elivulekileyo. Ikwakuphela kwesityalo se-Medical sonyango. I-teks isasazwa kwindawo enobushushu ye-hemisphere ye-hemisphere kwingingqi ye-subpical, malunga neentlobo ezili-11 emhlabeni. Kukho iintlobo ezi-4 kunye neendidi ezi-1 zase China, ezizezi mpuma mpuma, i-Yunnan Parks, iRhafu, iTibetus kunye neTarsis esemazantsi. Ezi ntlobo zintlanu zisasazwa emazantsi ntshona, eMzantsi China, eChina, eMpuma China, eMpuma China, North whowest China, eTaiwan. Izityalo zeTarsis ziqukethe iintlobo ezahlukeneyo zamacandelo eekhemikhali, kubandakanya iiteksti, i-flavonoids, i-liger, i-steroids, i-steroids, i-acitoc acids kunye ne-felycospedes. Irhafu ye-anti-tumor edumileyo (okanye i-paclimaxel) luhlobo lweetektani. Irhafu ineendlela ezizodwa ze-anticerisr. Irhafu inokuthi "Yikhulule" i-microrunugules ngokudibanisa nabo kwaye ikhusele i-microtubulles evela kwi-chromosomes ngexesha lokwahlulahlula iiseli, ngakumbi ukuqhuba ngokukhawuleza kweeseli zohlaza. Ngaphaya koko, ngokuvula i-macrophages, irhafu ibangela ukwehla kwi-TNF-α (i-tumar necrosis) i-receptor kunye nokukhululwa kwe-TNF-α, ukubulala iiseli ze-2]. Ngaphezu koko, irhafu inokuphembelela i-Apoptosis ngokwenza i-Apoptotic Pindoy Wally yendlela ye-Apoptotic Playpy ye-FAS / FASL okanye isebenze iNkqubo yeProjekthi yeCysteine [3]. Ngenxa yefuthe le-antikousr yayo ejolise kuyo, irhafu isetyenziswa ngokubanzi kunyango lwe-ovarian yomhlaza, umhlaza wamabele, umhlaza we-isclc, umhlaza we-gesiger, i-prostal yomhlaza, umhlaza wentamo, njl. Njl. Ingakumbi kumhlaza wamabele ophumeleleyo kunye nomhlaza ophambili we-ovarian, irhafu inemiphumo engathethekiyo, ngenxa yoko yaziwa ngokuba "ngumgca wokugqibela wokuzikhusela kunyango lomhlaza".
Irhafu lelona chiza lihle kakhulu le-anticyr kwimakethi yamanye amazwe kule minyaka idlulileyo kwaye ithathwa njengelinye lamachiza afanelekileyo abantu kwiminyaka engama-20 ezayo. Kwiminyaka yakutshanje, ngokukhula kwenani labemi kunye neziganeko zomhlaza, imfuno yerhafu ikwanda kakhulu. Okwangoku, irhafu efunekayo kuphando lweklinikhi okanye kwinzululwazi ikhutshiwe ngokuthe ngqo kwi-teks. Ngelishwa, umxholo werhafu kwizityalo usezantsi kakhulu. Umzekelo, umxholo werhafu yi-0.069% kwi-bark ye-teksi i-teksi ye-ruviflia, ethathwa njengowona mxholo uphakamileyo. Ukukhutshwa kwe-1 g yerhafu, ifuna malunga ne-13.6 kg ye-teks bark. Ngokusekwe kolu qikelelo, kuthatha i-3 - 12 yemithi engaphezulu kweminyaka eli-100 ubudala ukuba aphathe isigulana somhlaza wase-Ovarian. Ngenxa yoko, inani elikhulu lemithi ye-teksi sele inqunyulwe, ikhokelela ekuphelisweni kolu hlobo luxabisekileyo. Ukongeza, i-teks ihlwempuzeke kakhulu kwizibonelelo kwaye icotha ekukhuleni, okwenza ukuba kube nzima kuphuhliso kunye nokusetyenziswa kwerhafu.
Okwangoku, yonke i-synthesis yerhafu igqityiwe ngempumelelo. Nangona kunjalo, indlela yayo yokwenziwa inzima kakhulu kwaye ixabisa kakhulu, iyenza ukuba ingabaluleki. Indlela ye-Semi-Syntutic yerhafu ngoku ikhula ngokuvakalayo kwaye ithathwa njengento esebenzayo yokwandisa umthombo werhafu ukongeza kwizityalo zokutyala. Ngokufutshane, kwi-semi-synthesis yerhafu, i-fartsor preciormet ye-teks eninzi eninzi kwizityalo ze-teks ikhutshiwe kwaye iguqulwe ibe yirhafu ngeSynthesis Synthesis. Umxholo we-10-Deacetytybaccatin ⅲ kwiinaliti ze-teksi baccata zinokuba yi-0.1%. Kwaye iinaliti kulula ukuphinda ziphinde zithelekise ii-farks. Ke ngoko, i-semi-synthesis yerhafu esekwe kwi-10-deacetytybaccatin ye-10-deacetyty
Umzobo 1. Indlela ye-semi-syntatic yerhafu esekwe kwi-10-deacetytybaccatin ye-10
Kule posi, isityalo seerhafu sazihlanjululwa yi-flash sydy chromatographys yenkqubo yokwahlulahlula-hlulo-mali kwi-Propeding Cartridges eveliswe yiTechchIeges ye-SAntai. Imeko ekujolise kuyo kwimveliso ihlangabezane neemfuno zokucoceka ifunyenwe kwaye inokusetyenziswa kuphando lwezenzululwazi, inika isisombululo esisebenzayo sokuhlanjululwa ngokukhawuleza kolu hlobo lweemveliso zendalo.
| Isixhobo | Umatshini we-wandbean ™ | |
| Ikhatriji | I-12 g eyahlula i-clash cartridge (20), 100 å, inombolo yoku-odola inombolo: SW-5222-012-SP) | |
| Wavelength | I-254 NM (ihloliwe), i-280 NM (iliso) | |
| Isigaba sefowuni | I-Solvent A: Amanzi | |
| I-Solvent B: Metanol | ||
| Umgangatho wohambo | I-15 ml / min | |
| Isampulu yokulayisha | I-20 mg Raw isampulu inyibilikisiwe kwi-1 ML DMO | |
| Igradient | Ixesha (imiz) | I-Solvent B (%) |
| 0 | 10 | |
| 5 | 10 | |
| 7 | 28 | |
| 14 | 28 | |
| 16 | 40 | |
| 20 | 60 | |
| 27 | 60 | |
| 30 | 72 | |
| 40 | 72 | |
| 43 | I-100 | |
| 45 | I-100 | |
Iziphumo neengxoxo
I-flash chromatom ye-crude ikhupha kwi-teksi ibonisiwe kumzobo 2. Ngokuhlalutya i-chromatom, imveliso ekujoliswe kuyo kunye nokungcola okufunyenwe ukwahlulwa kwesiseko. Ngaphaya koko, ukuzala kwakhona kwazaliseka ngenaliti ezininzi zesampulu (idatha ayiboniswanga). Kuya kuthatha malunga neeyure ezi-4 ukugqiba ukwahlulwa kwendlela yencwadana ye-chromatography ngeikholamu zeglasi. Ukuthelekisa i-chromatography ye-chromatography ye-chromatography, indlela yokucoca ezenzekelayo kwesi sithuba kuphela ifuna kuphela imizuzu engama-44 yokugqibezela wonke umsebenzi wokucoca (njengoko kubonisiwe kumzobo 3). Ngaphezulu kwe-80% yexesha kunye nesixa esikhulu se-solvent sinokugcinwa ngokuthatha indlela ezenzekelayo, enokunciphisa ngokufanelekileyo iindleko kunye nokuphucula ukusebenza kakuhle.
Umzobo 2
Umzobo 3. Ukuthelekiswa kwencwadana ye-chromatography yendlela yokuthintela ngokuzenzekelayo.
Ukuqukumbela, ukudibanisa ngokwamasapflash C18 RP ye-Carridges ene-Waprids kunye noMatshini we-Eapben anokunikezela ngesisombululo esikhawulezayo nesifanelekileyo sokuhlanjwa okukhawulezayo njengeerhafu.
Izalathiso
I-1. I-Alsushin GM, i-Geer GC, i-Kellogg Eh, Zhang R, Baker Doods E. Iseli, 2014, 157 (5), 1117-1129.
I-2. I-Burkhart CA, Berman JW, Swindell Cs kunye neHorpetz sb. Ubudlelwane phakathi kwesakhiwo serhafu kunye nezinye iitektane ngokusungulwa kwe-tumor necrosis ye-tumo ye-α kunye ne-cytotocity. Uphando lomhlaza, 1994, 54 (22), 57797882.
I-3. Ipaki SJ, Wu Ch, Gordon Jd, Zhong X, Emami A kunye ne-safa. I-teks ifaka i-caspase-10-i-Apoptosis exhomekeke kwi-Apoptosis, uJ. Chem., 2004, 279, 51057-5067.
4. I-PaclimaXe. Umbutho waseMelika weSokhemesti yezeMpilo. [NgoJanuwari 2, 2015]
I-5. Bruce Gamnem kunye noRoland R. Franke. I-PaclitaXle kwiitekisi eziphambili: Imbono kwiNdawo yokuYila kwi-chemistry ye-organozircoin. J. Org. Chem., 2007, 72 (11), 3981-3987.
Kukho uthotho lwezahlulo ze-SP18 RP ye-carsh carridges eneenkcukacha ezahlukeneyo ezivela kwiTekhnoloji ye-SAntai (njengoko kubonisiwe kwiTheyibhile 2).
| Inombolo yento | Ubungakanani bekholamu | Umgangatho wohambo (ml / min) | Max.pressored (i-psi / bar) |
| SW-5222-004-SP | 5.4 g | 5-15 | I-400 / 27.5 |
| SW-5222-012-SP | I-20 g | I-10-25 | I-400 / 27.5 |
| SW-5222-025-SP | 33 g | I-10-25 | I-400 / 27.5 |
| SW-5222-040-SP | 48 g | I-15-30 | I-400 / 27.5 |
| SW-5222-080-SP | I-105 g | 25-50 | I-350 / 24.0 |
| I-SW-5222-120-SP | I-155 g | I-30-60 | I-300 / 20.7 |
| I-SW-522220-SP | I-300 g | 40-80 | I-300 / 20.7 |
| SW-5222-330-SP | I-420 g | 40-80 | I-250 / 17.2 |
Itheyibhile 2. Yahlula i-c18 rp carshids.
Izinto zokupakisha: Ukusebenza kakuhle kwe-C18-i-FiedIca, i-20 - 45 μm, 100 μm
Ngolwazi oluthe kratya malunga neenkcazo ezichaziweyo zomatshini we-Supben ™, okanye ulungelelwaniso lwe-odolo malunga ne-Prayflash Seripriges, nceda undwendwele iwebhusayithi yethu
IXESHA LOKUQALA: USep-20 ukuya ku-2008